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Vol. 13, Issue 10, 3576-3587, October 2002

and
*Junior Research Group of Molecular Cell Biology, Institute of
Environmental Health Research, Heinrich-Heine-University,
Düsseldorf, Germany; A prerequisite for proteins to interact in a cell is that they are
present in the same intracellular compartment. Although it is generally
accepted that proteasomes occur in both, the cytoplasm and the nucleus,
research has been focusing on cytoplasmic protein breakdown and antigen
processing, respectively. Thus, little is known on the functional
organization of the proteasome in the nucleus. Here we report that
within the nucleus 20S and 26S proteasomes occur throughout the
nucleoplasm and partially colocalize with splicing factor-containing
speckles. Because proteasomes are absent from the nucleolus, a
recruitment system was used to analyze the molecular fate of nucleolar
protein fibrillarin: Subtoxic concentrations of mercuric chloride
(HgCl2) induce subcellular redistribution of fibrillarin
and substantial colocalization (33%) with nucleoplasmic proteasomes in
different cell lines and in primary cells isolated from mercury-treated
mice. Accumulation of fibrillarin and fibrillarin-ubiquitin conjugates
in lactacystin-treated cells suggests that proteasome-dependent processing of this autoantigen occurs upon mercury induction. The
latter observation might constitute the cell biological basis of
autoimmune responses that specifically target fibrillarin in mercury-mouse models and scleroderma.
Department of Molecular
Biology, Institute of Molecular Biotechnology, Jena, Germany; and
Computing Center, Technical University, Aachen, Germany
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